Abstract
Background: The delivery of aerosolised chemotherapeutic substances into pressurised capnoperitonea has been reported to be more effective than conventional liquid chemotherapy for the treatment of peritoneal carcinomatosis. However, recent reports reveal limitations of the currently available technology.Material and Methods: A novel approach for pressurised intraperitoneal aerosol chemotherapy (PIPAC), called hyperthermic intracavitary nanoaerosol therapy (HINAT), based on extracavitary generation of hyperthermic and unipolar charged aerosols, was developed. The aerosol size distribution, the spatial drug distribution and in-tissue depth penetration of HINAT were studied by laser diffraction spectrometry, differential electrical mobility analysis, time of flight spectrometry, scintigraphic peritoneography and fluorescence microscopy. All experiments were performed contemporaneous with conventional PIPAC for the purpose of comparison. Furthermore, a first proof of concept was simulated in anesthetised German Landrace pigs.Results: HINAT provides a nanometre-sized (63 nm) unipolar-charged hyperthermic (41 °C) drug aerosol for quasi uniform drug deposition over the whole peritoneum with significantly deeper drug penetration than that offered by conventional PIPAC.
Highlights
Reliable epidemiologic data concerning the dissemination of peritoneal carcinomatosis (PC) are not available, but it is estimated that this stage of disease is diagnosed yearly for about 20,000 patients in Germany [1]
hyperthermic intracavitary nanoaerosol therapy (HINAT) provides a nanometre-sized (63 nm) unipolar-charged hyperthermic (41 °C) drug aerosol for quasi uniform drug deposition over the whole peritoneum with significantly deeper drug penetration than that offered by conventional Pressurised IntraPeritoneal Aerosol Chemotherapy (PIPAC)
In order to improve the application of chemotherapeutic drugs for the treatment of peritoneal carcinomatosis during pressurised intraperitoneal aerosol chemotherapy (PIPAC), a novel approach was developed
Summary
Reliable epidemiologic data concerning the dissemination of peritoneal carcinomatosis (PC) are not available, but it is estimated that this stage of disease is diagnosed yearly for about 20,000 patients in Germany [1]. In order to treat PC with adequately high doses of chemotherapeutic substances at minimal systemic toxicity, first approaches for locoregional/intracavitary chemotherapy (ICC) based on liquid drug instillation (LICC) were already developed about forty years ago [2,3,4]. One promising and upcoming approach to treat end-stage patients suffering from enhanced PC is the Pressurised IntraPeritoneal Aerosol Chemotherapy (PIPAC), where the drug-containing solution is aerosolised within a pressurised carbon-dioxide-based capnoperitoneum (i.e., with a carbondioxide-inflated abdominal cavity) by means of a microinjection pump (MIP®) in combination with a high-pressure injector. The delivery of aerosolised chemotherapeutic substances into pressurised capnoperitonea has been reported to be more effective than conventional liquid chemotherapy for the treatment of peritoneal carcinomatosis. Recent reports reveal limitations of the currently available technology
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